Novel Functions of Intracellular IL-1ra in Human Dermal Fibroblasts: Implications in the Pathogenesis of Fibrosis
Open accessAbstract
Intracellular IL-1 receptor antagonist (icIL-1ra) is reportedly involved in functions independent of blocking IL-1 receptor signaling. Fibroblasts derived from the involved skin of patients with systemic sclerosis (SSc) are predominantly of the myofibroblast phenotype, with higher levels of icIL-1ra compared to normal skin fibroblasts. We examined the effect of overexpression of icIL-1ra on the phenotype and function of normal fibroblasts with respect to the expression of alpha smooth muscle actin (alpha-SMA), a specific marker for myofibroblasts, and plasminogen activator inhibitor (PAI), a protein involved in fibrogenesis and expressed at higher levels in myofibroblasts, and the production of collagenase (matrix metalloproteinase-1 (MMP-1)), the major enzyme involved in the degradation of native collagen in the skin. Normal human foreskin fibroblasts overexpressing icIL-1ra showed higher levels of alpha-SMA and PAI and had lower levels of collagenase and MMP-1 mRNA induced by inflammatory cytokines. By contrast, levels of mRNA for tissue inhibitor of metalloproteinase-1 in the transfected cells were not different from the control cells. Pretreatment of the ic-IL-1ra-transfected cells with antisense oligonucleotide directed against the mRNA of icIL-1ra restored MMP-1 expression induced by stimulation with IL-1beta. Our data indicate novel functions for icIL-1ra, which might be relevant to the genesis of fibrotic diseases such as SSc.
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Fibroblasts and keratinocytes are known to express intracellular isoforms of IL-1Ra.
“fibroblasts and keratinocytes, that are known to express intracellular isoforms of IL-1Ra [28, 29]”
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VAI TRÒ CỦA GIA ĐÌNH INTERLEUKIN-1 TRONG KIỂU HÌNH XƠ HÓA Ở BỆNH NHÂN XƠ CỨNG BÌ HỆ THỐNG
Ngọc, P. T. (2022) · Tạp chí Da liễu học Việt Nam · doi:10.56320/tcdlhvn.37.29
- Authors
- Kanangat, S., Postlethwaite, A. E., Higgins, G. C., & Hasty, K. A.
- Affiliations
- University of Tennessee Health Science Center (US)
- Corresponding author
- Hasty, Karen A.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 126
- Issue
- 4
- Pages
- 756-765
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2025298638
- Cited by
- 36
- References
- 50
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 1 · 2012: 1
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (I-P50 AR44890, P50AR044890)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
- Keywords
- systemic sclerosis, dermal fibroblasts, myofibroblasts, alpha-smooth muscle actin, plasminogen activator inhibitor, MMP-1, collagenase, TIMP-1, IL-1β, fibrosis, antisense oligonucleotides, skin fibrosis
- MeSH terms
- Actins, Fibroblasts, Fibrosis, Humans, Phenotype, Scleroderma, Systemic, Sialoglycoproteins, Skin, Tumor Necrosis Factor-alpha, Transcriptional Activation, Plasminogen Inactivators, Tissue Inhibitor of Metalloproteinase-1, Oligodeoxyribonucleotides, Antisense, Dermis, Matrix Metalloproteinase 1, Interleukin 1 Receptor Antagonist Protein
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